TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21929	66010;66011;66012	chr2:178583018;178583017;178583016	chr2:179447745;179447744;179447743
N2AB	20288	61087;61088;61089	chr2:178583018;178583017;178583016	chr2:179447745;179447744;179447743
N2A	19361	58306;58307;58308	chr2:178583018;178583017;178583016	chr2:179447745;179447744;179447743
N2B	12864	38815;38816;38817	chr2:178583018;178583017;178583016	chr2:179447745;179447744;179447743
Novex-1	12989	39190;39191;39192	chr2:178583018;178583017;178583016	chr2:179447745;179447744;179447743
Novex-2	13056	39391;39392;39393	chr2:178583018;178583017;178583016	chr2:179447745;179447744;179447743
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-125
• Domain position: 64
• Structural Position: 148
• Q(SASA): 0.7261
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
K/R	rs1465791266	0.409	0.998	N	0.551	0.153	0.192905019026	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	6.52E-05	0	None	0	0	None	0	None	0	0	0
K/R	rs1465791266	0.409	0.998	N	0.551	0.153	0.192905019026	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
K/R	rs1465791266	0.409	0.998	N	0.551	0.153	0.192905019026	gnomAD-4.0.0	5.17072E-06	None	None	None	None	N	None	6.79094E-05	0	None	0	0	None	0	0	0	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
K/A	0.2931	likely_benign	0.2914	benign	0.051	Stabilizing	0.994	D	0.497	neutral	None	None	None	None	N
K/C	0.7109	likely_pathogenic	0.6732	pathogenic	-0.126	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
K/D	0.4991	ambiguous	0.4937	ambiguous	-0.053	Destabilizing	0.999	D	0.558	neutral	None	None	None	None	N
K/E	0.1813	likely_benign	0.1729	benign	-0.069	Destabilizing	0.996	D	0.525	neutral	N	0.368450629	None	None	N
K/F	0.8054	likely_pathogenic	0.7691	pathogenic	-0.294	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
K/G	0.382	ambiguous	0.3804	ambiguous	-0.099	Destabilizing	0.997	D	0.503	neutral	None	None	None	None	N
K/H	0.3297	likely_benign	0.3153	benign	-0.367	Destabilizing	1.0	D	0.605	neutral	None	None	None	None	N
K/I	0.4141	ambiguous	0.3821	ambiguous	0.362	Stabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
K/L	0.4033	ambiguous	0.3693	ambiguous	0.362	Stabilizing	1.0	D	0.499	neutral	None	None	None	None	N
K/M	0.2533	likely_benign	0.2324	benign	0.21	Stabilizing	1.0	D	0.605	neutral	N	0.502154194	None	None	N
K/N	0.3515	ambiguous	0.3482	ambiguous	0.319	Stabilizing	0.999	D	0.612	neutral	N	0.438641433	None	None	N
K/P	0.8004	likely_pathogenic	0.7826	pathogenic	0.284	Stabilizing	1.0	D	0.624	neutral	None	None	None	None	N
K/Q	0.1336	likely_benign	0.1292	benign	0.129	Stabilizing	0.999	D	0.646	neutral	N	0.430003307	None	None	N
K/R	0.0852	likely_benign	0.0829	benign	0.056	Stabilizing	0.998	D	0.551	neutral	N	0.439969585	None	None	N
K/S	0.3398	likely_benign	0.3388	benign	-0.108	Destabilizing	0.927	D	0.33	neutral	None	None	None	None	N
K/T	0.1692	likely_benign	0.1665	benign	0.006	Stabilizing	0.992	D	0.549	neutral	N	0.434678408	None	None	N
K/V	0.3689	ambiguous	0.3477	ambiguous	0.284	Stabilizing	1.0	D	0.581	neutral	None	None	None	None	N
K/W	0.7924	likely_pathogenic	0.7489	pathogenic	-0.358	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
K/Y	0.7	likely_pathogenic	0.6614	pathogenic	0.012	Stabilizing	1.0	D	0.64	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.